Hepatic glucose disposition during concomitant portal glucose and amino acid infusions in the dog

1998 ◽  
Vol 274 (5) ◽  
pp. E893-E902 ◽  
Author(s):  
Mary Courtney Moore ◽  
Paul J. Flakoll ◽  
Po-Shiuan Hsieh ◽  
Michael J. Pagliassotti ◽  
Doss W. Neal ◽  
...  
Keyword(s):  
Amino Acid ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Experimental Period ◽  
Hepatic Glycogen ◽  
Blood Concentrations ◽  
Amino Acid Infusion ◽  
Arterial Blood ◽  
Hepatic Glucose ◽  
Hepatic Glucose Uptake

The effect of concomitant intraportal infusion of glucose and gluconeogenic amino acids (AA) on net hepatic glucose uptake (NHGU) and glycogen synthesis was examined in 42-h-fasted dogs. After a basal period, there was a 240-min experimental period during which somatostatin was infused continuously into a peripheral vein and insulin and glucagon (at 3-fold basal and basal rates, respectively) and glucose (18.3 μmol ⋅ kg−1⋅ min−1) were infused intraportally. One group (PoAA, n = 7) received an AA mixture intraportally at 7.6 μmol ⋅ kg−1⋅ min−1, whereas the other group (NoAA, n = 6) did not receive AA. Arterial blood glucose concentrations and hepatic glucose loads were the same in the two groups. NHGU averaged 4.8 ± 2.0 (PoAA) and 9.4 ± 2.0 (NoAA) μmol ⋅ kg−1⋅ min−1( P < 0.05), and tracer-determined hepatic glucose uptake was 4.6 ± 1.6 (PoAA) and 10.0 ± 1.7 (NoAA) μmol ⋅ kg−1⋅ min−1( P < 0.05). AA data for PoAA and NoAA, respectively, were as follows: arterial blood concentrations, 1,578 ± 133 vs. 1,147 ± 86 μM ( P < 0.01); hepatic loads, 56 ± 3 vs. 32 ± 4 μmol ⋅ kg−1⋅ min−1( P < 0.01); and net hepatic uptakes, 14.1 ± 1.4 vs. 5.6 ± 0.4 μmol ⋅ kg−1⋅ min−1( P < 0.01). The rate of net hepatic glycogen synthesis was 7.5 ± 1.9 (PoAA) vs. 10.7 ± 2.3 (NoAA) μmol ⋅ kg−1⋅ min−1( P = 0.1). In a net sense, intraportal gluconeogenic amino acid delivery directed glucose carbon away from the liver. Despite this, net hepatic carbon uptake was equivalent in the presence and absence of amino acid infusion.

Differential effect of amino acid infusion route on net hepatic glucose uptake in the dog

1999 ◽  
Vol 276 (2) ◽  
pp. E295-E302 ◽  
Author(s):  
Mary Courtney Moore ◽  
Po-Shiuan Hsieh ◽  
Paul J. Flakoll ◽  
Doss W. Neal ◽  
Alan D. Cherrington
Keyword(s):  
Amino Acid ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Hepatic Glycogen ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Arterial Blood ◽  
Hepatic Glucose ◽  
Hepatic Glucose Uptake ◽  
Portal Infusion

Concomitant portal infusion of gluconeogenic amino acids (GNGAA) and glucose significantly reduces net hepatic glucose uptake (NHGU), in comparison with NHGU during portal infusion of glucose alone. To determine whether this effect on NHGU is specific to the portal route of GNGAA delivery, somatostatin, intraportal insulin (3-fold basal) and glucagon (basal), and intraportal glucose (to increase the hepatic glucose load by ∼50%) were infused for 240 min. GNGAA were infused peripherally into a group of dogs (PeAA), at a rate to match the hepatic GNGAA load in a group of dogs that were given the same GNGAA mixture intraportally (PoAA) at 7.6 μmol ⋅ kg−1 ⋅ min−1(9). The arterial blood glucose concentrations and hepatic glucose loads were the same in the two groups, but NHGU (−0.9 ± 0.2 PoAA and −2.1 ± 0.5 mg ⋅ kg−1 ⋅ min−1in PeAA, P < 0.05) and net hepatic fractional extraction of glucose (2.6 ± 0.7% in PoAA vs. 5.9 ± 1.4% in PeAA, P < 0.05) differed. Neither the hepatic loads nor the net hepatic uptakes of GNGAA were significantly different in the two groups. Net hepatic glycogen synthesis was ∼2.5-fold greater in PeAA than PoAA ( P < 0.05). Intraportal, but not peripheral, amino acid infusion suppresses NHGU and net hepatic glycogen synthesis in response to intraportal glucose infusion.

Inclusion of low amounts of fructose with an intraportal glucose load increases net hepatic glucose uptake in the presence of relative insulin deficiency in dog

2005 ◽  
Vol 288 (6) ◽  
pp. E1160-E1167 ◽  
Author(s):  
Masakazu Shiota ◽  
Pietro Galassetti ◽  
Kayano Igawa ◽  
Doss W. Neal ◽  
Alan D. Cherrington
Keyword(s):  
Blood Glucose ◽  
Glucose Uptake ◽  
Control Period ◽  
Glucose Infusion ◽  
Control Group ◽  
Hepatic Glycogen ◽  
Arterial Blood ◽  
Hepatic Glucose ◽  
Arterial Blood Glucose ◽  
Hepatic Glucose Uptake

The effect of small amounts of fructose on net hepatic glucose uptake (NHGU) during hyperglycemia was examined in the presence of insulinopenia in conscious 42-h fasted dogs. During the study, somatostatin (0.8 μg·kg−1·min−1) was given along with basal insulin (1.8 pmol·kg−1·min−1) and glucagon (0.5 ng·kg−1·min−1). After a control period, glucose (36.1 μmol·kg−1·min−1) was continuously given intraportally for 4 h with (2.2 μmol·kg−1·min−1) or without fructose. In the fructose group, the sinusoidal blood fructose level (nmol/ml) rose from <16 to 176 ± 11. The infusion of glucose alone (the control group) elevated arterial blood glucose (μmol/ml) from 4.3 ± 0.3 to 11.2 ± 0.6 during the first 2 h after which it remained at 11.6 ± 0.8. In the presence of fructose, glucose infusion elevated arterial blood glucose (μmol/ml) from 4.3 ± 0.2 to 7.4 ± 0.6 during the first 1 h after which it decreased to 6.1 ± 0.4 by 180 min. With glucose infusion, net hepatic glucose balance (μmol·kg−1·min−1) switched from output (8.9 ± 1.7 and 13.3 ± 2.8) to uptake (12.2 ± 4.4 and 29.4 ± 6.7) in the control and fructose groups, respectively. Average NHGU (μmol·kg−1·min−1) and fractional glucose extraction (%) during last 3 h of the test period were higher in the fructose group (30.6 ± 3.3 and 14.5 ± 1.4) than in the control group (15.0 ± 4.4 and 5.9 ± 1.8). Glucose 6-phosphate and glycogen content (μmol glucose/g) in the liver and glucose incorporation into hepatic glycogen (μmol glucose/g) were higher in the fructose (218 ± 2, 283 ± 25, and 109 ± 26, respectively) than in the control group (80 ± 8, 220 ± 31, and 41 ± 5, respectively). In conclusion, small amounts of fructose can markedly reduce hyperglycemia during intraportal glucose infusion by increasing NHGU even when insulin secretion is compromised.

scholarly journals A physiological increase in the hepatic glycogen level does not affect the response of net hepatic glucose uptake to insulin

2009 ◽  
Vol 297 (2) ◽  
pp. E358-E366 ◽  
Author(s):  
Jason J. Winnick ◽  
Zhibo An ◽  
Mary Courtney Moore ◽  
Christopher J. Ramnanan ◽  
Ben Farmer ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Control Period ◽  
In Vivo Studies ◽  
Hepatic Glycogen ◽  
Glycogen Level ◽  
Hepatic Glucose ◽  
Glycogen Deposition ◽  
Hepatic Glucose Uptake

To determine the effect of an acute increase in hepatic glycogen on net hepatic glucose uptake (NHGU) and disposition in response to insulin in vivo, studies were performed on two groups of dogs fasted 18 h. During the first 4 h of the study, somatostatin was infused peripherally, while insulin and glucagon were replaced intraportally in basal amounts. Hyperglycemia was brought about by glucose infusion, and either saline ( n = 7) or fructose ( n = 7; to stimulate NHGU and glycogen deposition) was infused intraportally. A 2-h control period then followed, during which the portal fructose and saline infusions were stopped, allowing NHGU and glycogen deposition in the fructose-infused animals to return to rates similar to those of the animals that received the saline infusion. This was followed by a 2-h experimental period, during which hyperglycemia was continued but insulin infusion was increased fourfold in both groups. During the initial 4-h glycogen loading period, NHGU averaged 1.18 ± 0.27 and 5.55 ± 0.53 mg·kg−1·min−1 and glycogen synthesis averaged 0.72 ± 0.24 and 3.98 ± 0.57 mg·kg−1·min−1 in the saline and fructose groups, respectively ( P < 0.05). During the 2-h hyperinsulinemic period, NHGU rose from 1.5 ± 0.4 and 0.9 ± 0.2 to 3.1 ± 0.6 and 2.5 ± 0.5 mg·kg−1·min−1 in the saline and fructose groups, respectively, a change of 1.6 mg·kg−1·min−1 in both groups despite a significantly greater liver glycogen level in the fructose-infused group. Likewise, the metabolic fate of the extracted glucose (glycogen, lactate, or carbon dioxide) was not different between groups. These data indicate that an acute physiological increase in the hepatic glycogen content does not alter liver glucose uptake and storage under hyperglycemic/hyperinsulinemic conditions in the dog.

Effects of hyperglycemia on hepatic gluconeogenic flux during glycogen phosphorylase inhibition in the conscious dog

2004 ◽  
Vol 286 (4) ◽  
pp. E510-E522 ◽  
Author(s):  
Dale S. Edgerton ◽  
Sylvain Cardin ◽  
Doss Neal ◽  
Ben Farmer ◽  
Margaret Lautz ◽  
...  
Keyword(s):  
Glycogen Phosphorylase ◽  
Glycogen Synthesis ◽  
Experimental Period ◽  
Hepatic Uptake ◽  
Glycolytic Flux ◽  
Control Group ◽  
Hepatic Glycogen ◽  
Hepatic Glucose ◽  
Hepatic Glucose Uptake ◽  
Glycogen Breakdown

The aim of these studies was to investigate the effect of hyperglycemia with or without hyperinsulinemia on hepatic gluconeogenic flux, with the hypothesis that inhibition would be greatest with combined hyperglycemia/hyperinsulinemia. A glycogen phosphorylase inhibitor (BAY R3401) was used to inhibit glycogen breakdown in the conscious overnight-fasted dog, and the effects of a twofold rise in plasma glucose level (HI group) accompanied by 1) euinsulinemia (HG group) or 2) a fourfold rise in plasma insulin were assessed over a 5-h experimental period. Hormone levels were controlled using somatostatin with portal insulin and glucagon infusion. In the HG group, net hepatic glucose uptake and net hepatic lactate output substantially increased. There was little or no effect on the net hepatic uptake of gluconeogenic precursors other than lactate (amino acids and glycerol) or on the net hepatic uptake of free fatty acids compared with the control group. Consequently, whereas hyperglycemia had little effect on gluconeogenic flux to glucose 6-phosphate (G-6- P), net hepatic gluconeogenic flux was reduced because of increased hepatic glycolytic flux during hyperglycemia. Net hepatic glycogen synthesis was increased by hyperglycemia. The effect of hyperglycemia on gluconeogenic flux to G-6- P and net hepatic gluconeogenic flux was similar. We conclude that, in the absence of appreciable glycogen breakdown, the increase in glycolytic flux that accompanies hyperglycemia results in decreased net carbon flux to G-6- P but no effect on gluconeogenic flux to G-6- P.

Neural and pancreatic influences on net hepatic glucose uptake and glycogen synthesis

1996 ◽  
Vol 271 (2) ◽  
pp. E215-E222 ◽  
Author(s):  
M. C. Moore ◽  
L. Rossetti ◽  
M. J. Pagliassotti ◽  
M. Monahan ◽  
C. Venable ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Area Under The Curve ◽  
Glucose Infusion ◽  
Hepatic Glycogen ◽  
Fourfold Increase ◽  
Direct Pathway ◽  
Hepatic Glucose ◽  
Hepatic Glucose Uptake ◽  
Liver Nerves

The role of the liver nerves in the disposition of peripherally administered glucose was examined in seven hepatic innervated (HI) and nine hepatic denervated (HD) 42-h-fasted conscious dogs. After a 40-min basal period, there was a 4-h experimental period during which the hepatic glucose load was increased twofold via peripheral glucose infusion. Somatostatin was infused to suppress pancreatic endocrine secretion, and insulin and glucagon were infused intraportally to produce a fourfold increase in insulin and a gradual decrease (approximately 25%) in glucagon. The area under the curve of net hepatic glucose uptake (NHGU) during the glucose infusion period totaled 483 +/- 82 and 335 +/- 32 mg/kg in HD and HI, respectively (P < 0.05). The area under the curve of the hepatic fractional extraction of glucose was 27% greater in HD (P < 0.05). Net hepatic lactate output was similar in the two groups, and net hepatic glycogen synthesis was 3.8 +/- 0.8 vs. 2.7 +/- 0.5 mg.kg dog wt-1.min-1 in HD and HI, respectively (P = 0.13). The direct pathway of glycogen synthesis was responsible for 54-58% of net hepatic glycogen synthesis in both HI and HD (n = 6 for both). In summary 1) NHGU in response to peripheral glucose infusion was approximately 44% greater in HD than in HI, 2) net hepatic glycogen synthesis was enhanced by 41% in HD although the probability of this change was 0.13, and 3) the contribution of the direct pathway to glycogen synthesis was the same in HD and HI. These data are consistent with a role for the liver nerves in regulating the magnitude of NHGU in response to glucose administration. They also indicate that the absence of liver nerves may reduce glycogen turnover during glucose infusion.

scholarly journals Nonhepatic response to portal glucose delivery in conscious dogs

2000 ◽  
Vol 279 (6) ◽  
pp. E1271-E1277 ◽  
Author(s):  
Mary Courtney Moore ◽  
Po-Shiuan Hsieh ◽  
Doss W. Neal ◽  
Alan D. Cherrington
Keyword(s):  
Glucose Uptake ◽  
Glucose Infusion ◽  
Glucose Load ◽  
Arterial Blood ◽  
Hepatic Glucose ◽  
The Difference ◽  
Arterial Plasma ◽  
Arterial Blood Glucose ◽  
Blood Glucose Concentrations ◽  
Hepatic Glucose Uptake

The glycemic and hormonal responses and net hepatic and nonhepatic glucose uptakes were quantified in conscious 42-h-fasted dogs during a 180-min infusion of glucose at 10 mg · kg−1 · min−1 via a peripheral (Pe10, n = 5) or the portal (Po10, n = 6) vein. Arterial plasma insulin concentrations were not different during the glucose infusion in Pe10 and Po10 (37 ± 6 and 43 ± 12 μU/ml, respectively), and glucagon concentrations declined similarly throughout the two studies. Arterial blood glucose concentrations during glucose infusion were not different between groups (125 ± 13 and 120 ± 6 mg/dl in Pe10 and Po10, respectively). Portal glucose delivery made the hepatic glucose load significantly greater (36 ± 3 vs. 46 ± 5 mg · kg−1 · min−1 in Pe10 vs. Po10, respectively, P < 0.05). Net hepatic glucose uptake (NHGU; 1.1 ± 0.4 vs. 3.1 ± 0.4 mg · kg−1 · min−1) and fractional extraction (0.03 ± 0.01 vs. 0.07 ± 0.01) were smaller ( P < 0.05) in Pe10 than in Po10. Nonhepatic (primarily muscle) glucose uptake was correspondingly increased in Pe10 compared with Po10 (8.9 ± 0.4 vs. 6.9 ± 0.4 mg · kg−1 · min−1, P < 0.05). Approximately one-half of the difference in NHGU between groups could be accounted for by the difference in hepatic glucose load, with the remainder attributable to the effect of the portal signal itself. Even in the absence of somatostatin and fixed hormone concentrations, the portal signal acts to alter partitioning of a glucose load among the tissues, stimulating NHGU and reducing peripheral glucose uptake.

Rapid reversal of the effects of the portal signal under hyperinsulinemic conditions in the conscious dog

1999 ◽  
Vol 276 (5) ◽  
pp. E930-E937 ◽  
Author(s):  
Po-Shiuan Hsieh ◽  
Mary Courtney Moore ◽  
Doss W. Neal ◽  
Maya Emshwiller ◽  
Alan D. Cherrington
Keyword(s):  
Glucose Uptake ◽  
Infusion Rate ◽  
Experimental Period ◽  
Glucose Infusion ◽  
Glucose Load ◽  
Conscious Dog ◽  
The Third ◽  
Hepatic Glucose ◽  
Rapid Reversal ◽  
Hepatic Glucose Uptake

Experiments were performed on two groups of 42-h-fasted conscious dogs ( n = 6/group). Somatostatin was given peripherally with insulin (4-fold basal) and glucagon (basal) intraportally. In the first experimental period, glucose was infused peripherally to double the hepatic glucose load (HGL) in both groups. In the second experimental period, glucose (21.8 μmol ⋅ kg−1⋅ min−1) was infused intraportally and the peripheral glucose infusion rate (PeGIR) was reduced to maintain the precreating HGL in the portal signal (PO) group, whereas saline was given intraportally in the control (CON) group and PeGIR was not changed. In the third period, the portal glucose infusion was stopped in the PO group and PeGIR was increased to sustain HGL. PeGIR was continued in the CON group. The glucose loads to the liver did not differ in the CON and PO groups. Net hepatic glucose uptake was 9.6 ± 2.5, 11.6 ± 2.6, and 15.5 ± 3.2 vs. 10.8 ± 1.8, 23.7 ± 3.0, and 15.5 ± 1.1 μmol ⋅ kg−1⋅ min−1, and nonhepatic glucose uptake (non-HGU) was 29.8 ± 1.1, 40.1 ± 4.5, and 49.5 ± 4.0 vs. 26.6 ± 4.3, 23.2 ± 4.0, and 40.4 ± 3.1 μmol ⋅ kg−1⋅ min−1in the CON and PO groups during the three periods, respectively. Cessation of the portal signal shifted NHGU and non-HGU to rates similar to those evident in the CON group within 10 min. These results indicate that even under hyperinsulinemic conditions the effects of the portal signal on hepatic and peripheral glucose uptake are rapidly reversible.

Hepatic glucose metabolism during intraduodenal glucose infusion: impact of infection

2000 ◽  
Vol 279 (1) ◽  
pp. E108-E115
Author(s):  
Owen P. McGuinness ◽  
Joseph Ejiofor ◽  
D. Brooks Lacy ◽  
Nancy Schrom
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Fibrin Clot ◽  
Glucose Absorption ◽  
Glucose Infusion ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose ◽  
Glycogen Deposition ◽  
Hepatic Glucose Uptake

We previously reported that infection decreases hepatic glucose uptake when glucose is given as a constant peripheral glucose infusion (8 mg · kg−1· min−1). This impairment persisted despite greater hyperinsulinemia in the infected group. In a normal setting, hepatic glucose uptake can be further enhanced if glucose is given gastrointestinally. Thus the aim of this study was to determine whether hepatic glucose uptake is impaired during an infection when glucose is given gastrointestinally. Thirty-six hours before study, a sham (SH, n = 7) or Escherichia coli-containing (2 × 109organisms/kg; INF; n = 7) fibrin clot was placed in the peritoneal cavity of chronically catheterized dogs. After the 36 h, a glucose bolus (150 mg/kg) followed by a continuous infusion (8 mg · kg−1· min−1) of glucose was given intraduodenally to conscious dogs for 240 min. Tracer ([3-3H]glucose and [U-14C]glucose) and arterial-venous difference techniques were used to assess hepatic and intestinal glucose metabolism. Infection increased hepatic blood flow (35 ± 5 vs. 47 ± 3 ml · kg−1· min−1; SH vs. INF) and basal glucose rate of appearance (2.1 ± 0.2 vs. 3.3 ± 0.1 mg · kg−1· min−1). Arterial insulin concentrations increased similarly in SH and INF during the last hour of glucose infusion (38 ± 8 vs. 46 ± 20 μU/ml), and arterial glucagon concentrations fell (62 ± 14 to 30 ± 3 vs. 624 ± 191 to 208 ± 97 pg/ml). Net intestinal glucose absorption was decreased in INF, attenuating the increase in blood glucose caused by the glucose load. Despite this, net hepatic glucose uptake (1.6 ± 0.8 vs. 2.4 ± 0.9 mg · kg−1· min−1; SH vs. INF) and consequently tracer-determined glycogen synthesis (1.3 ± 0.3 vs. 1.0 ± 0.3 mg · kg−1· min−1) were similar between groups. In summary, infection impairs net glucose absorption, but not net hepatic glucose uptake or glycogen deposition, when glucose is given intraduodenally.

Prior exercise increases net hepatic glucose uptake during a glucose load

1999 ◽  
Vol 276 (6) ◽  
pp. E1022-E1029 ◽  
Author(s):  
Pietro Galassetti ◽  
Robert H. Coker ◽  
Drury B. Lacy ◽  
Alan D. Cherrington ◽  
David H. Wasserman
Keyword(s):  
Portal Vein ◽  
Glucose Uptake ◽  
Control Period ◽  
Vena Cava ◽  
Experimental Period ◽  
Glucose Infusion ◽  
Glucose Load ◽  
Prior Exercise ◽  
Hepatic Glucose ◽  
Hepatic Glucose Uptake

The aim of these studies was to determine whether prior exercise enhances net hepatic glucose uptake (NHGU) during a glucose load. Sampling catheters (carotid artery, portal, hepatic, and iliac veins), infusion catheters (portal vein and vena cava), and Doppler flow probes (portal vein, hepatic and iliac arteries) were implanted. Exercise (150 min; n = 6) or rest ( n = 6) was followed by a 30-min control period and a 100-min experimental period (3.5 mg ⋅ kg−1⋅ min−1of glucose in portal vein and as needed in vena cava to clamp arterial blood glucose at ∼130 mg/dl). Somatostatin was infused, and insulin and glucagon were replaced intraportally at fourfold basal and basal rates, respectively. During experimental period the arterial-portal venous (a-pv) glucose gradient (mg/dl) was −18 ± 1 in sedentary and −19 ± 1 in exercised dogs. Arterial insulin and glucagon were similar in the two groups. Net hepatic glucose balance (mg ⋅ kg−1⋅ min−1) shifted from 1.9 ± 0.2 in control period to −1.8 ± 0.2 (negative rates represent net uptake) during experimental period in sedentary dogs (Δ3.7 ± 0.5); with prior exercise it shifted from 4.1 ± 0.3 ( P < 0.01 vs. sedentary) in control period to −3.2 ± 0.4 ( P < 0.05 vs. sedentary) during experimental period (Δ7.3 ± 0.7, P < 0.01 vs. sedentary). Net hindlimb glucose uptake (mg/min) was 4 ± 1 in sedentary animals in control period and 13 ± 2 during experimental period; in exercised animals it was 7 ± 1 in control period ( P < 0.01 vs. sedentary) and 32 ± 4 ( P < 0.01 vs. sedentary) during experimental period. As the total glucose infusion rate (mg ⋅ kg−1⋅ min−1) was 7 ± 1 in sedentary and 11 ± 1 in exercised dogs, ∼30% of the added glucose infusion due to prior exercise could be accounted for by the greater NHGU. In conclusion, when determinants of hepatic glucose uptake (insulin, glucagon, a-pv glucose gradient, glycemia) are controlled, prior exercise increases NHGU during a glucose load due to an effect that is intrinsic to the liver. Increased glucose disposal in the postexercise state is therefore due to an improved ability of both liver and muscle to take up glucose.

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